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Fig. 1 | Critical Care

Fig. 1

From: Infectious disease-associated encephalopathies

Fig. 1

Inflammatory signaling pathways to the brain. Systemic inflammation caused by pathogens, including viruses, bacteria, and parasites, leads to neuroinflammation with consequent cognitive and behavior impairments. The central nervous system is able to recognize systemic inflammation through (1) BBB dysfunction, with activation and apoptosis of endothelial cells, allowing cytokines and immune cells to invade the brain parenchyma; (2) the humoral pathway and saturable transport system in the blood–brain barrier (BBB), which involves the circumventricular organs (CVOs) and the choroid plexus, as local macrophage-like cells express innate immune receptors that recognize pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and cytokines, allowing inflammatory mediators to access the brain by volume diffusion and through cytokine-saturable transporters, since the CVOs do not have an intact BBB; (3) through activation of the afferent nerves (including the vagal nerves in abdominal/visceral infections and the trigeminal nerve in oro-lingual infections) by cytokines; and (4) IL-1β pathway signaling, through activation of IL-1 receptors expressed in perivascular macrophages and endothelial cells located in the brain microvasculature, initiating a local immune response

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